Heterologous expression of Pyrenocine A from <i>Colletotrichum gloeosporioides</i> CGMCC 3.17371

Pyrenocine A is a pyranone derivative known for its antiviral, antibacterial, and anti-cancer cell proliferation activities. Through genomic mining, we successfully identified the gene cluster responsible for the biosynthesis of pyrenocine A in <i>Colletotrichum gloeosporioides</i> CGMCC 3.17371. Six compounds were isolated through heterologous expression, which allowed us to elucidate the biosynthetic pathway of pyrenocine A <i>in vivo</i>. The identification of this gene cluster may provide a platform for metabolic engineering approaches to optimise pyrenocine A production. Notably, biological evaluations revealed that pyrenocine A and its derivative exhibited potent cytotoxicity against three human cancer cell lines (DLD-1, U-87MG, and U251) <i>in vitro</i>. These findings strongly suggest their therapeutic potential as novel anticancer agents, particularly for malignancies that demonstrate resistance to conventional treatments.